History:

• Family history positive for breast cancer (one aunt had breast cancer before the age of 30, grandfather had lung cancer, both two were mother‘s relatives).
• Without symptoms of disease but lost of weight for 2 kg (related to the stress due to the diagnosis of cancer).
• No pain or use of analgesics.

Physical examination:

• ECOG PS 0, 
• operative scar with no signs of infection, right breast without palpable lumps,
• physical examination: NAD

Blood tests:

• Within the normal range including tumor marker CA15-3

DIAGNOSIS: 
primary metastatic hormone positive, HER2 negative breast cancer with bone metastates

NAD – no abnormalities detected
 

Treatment goal: to prolong survival and maintain good quality of life.

8/2018: 1st line therapy with letrozol 2.5 mg/day and ribociclib 600 mg/day 3 weeks on, 1 week off were introduced until progressive disease or unacceptable toxicity.

ECG before the beginning of the treatment: within the normal range including the lenght of QT interval

Patient monitoring strategy: 
First two months follow up visit every two weeks, then monthly up to 6 months
 

Follow up at the start of 1b, 2a, 2b and 3rd cycle (10/10/2018) within normal limits

Follow up visit at the beginning of 4th cycle (7/11/2018): 

• History and physical examination NAD,
• blood results: hepatopathy grade 4 – ribociclib but not letrozole discontinued, 
• consultation with gastroenterologist: viral hepatitis tests and tests for autoimmune hepatitis ordered (both negative), follow up visit after 1 week
   

Subsequent liver tests:

Units:

• AST, ALT, gamma GT, alkaine phosphatase: μkat/l
• bilirubin:μ mol/l

13/11: discontinuation of all drugs

19/11: the patient became symptomatic: jaundice, fatigue, loss of appetite and weight:

• MRI of liver: parenchymal liver damage with signs of sinusoidal obstruction syndrome,
• metylprednisolone 1 mg/kg for 7 days introduced without significant improvement of liver tests
• Liver biopsy was not indicated as the result will not influence treatment decision,
• synthesis liver function was only moderately impaired (slightly pathologic INR and albumin levels)
• Supportive care: caloric supplements, osmotic laxatives to achieve loose stools

1/2019: symptoms improved to normal

• CA15-3 negative
• bone scintigraphy: stable disease

30/1/2019: introduction of anastrozole 1 mg/day 

• Liver tests remained normal,
• 2/2019: zoledronic acid 4 mg i.v. every three months due to bone metastases was introduced

10/2019 the patient without symptoms, CT scans (thorax, abdomen): stable disease

Genetic tests:

• no germline mutations,
• PIK3CA mutation found in primary tumor 
• Wild type dihydropyrimidine dehydrogenase gene → normal metabolism of fluorouracil
   

1. 1/2019 – 12/2021 anastrozole: stable disease until progression in bones - 3 years
2. 1/2022 – 4/2022 fulvestrant 500 mg i.m. monthly and alpelisib 300 mg/day: progressive disease in bones - 4 months
3. 5/2022 – 9/2022 exemestane 25 mg/day and everolimus 10 mg/day: - 5 months

• The dose of everolimus reduced to 5 mg/day due to transient hepatopathy grade 2
•  progessive disease in bones

4. 10/2022 till present: capecitabine: stable disease - 4 months

• The patient suffered from grade 4 hepatopathy due to ribociclib which was luckily reversible and left no consequences.
• Different CDK4/6 inhibitor was not introduced due to severity of the hepatopathy.
• The disease had indolent course initially but did not respond to two lines of further endocrine therapy → NGS sequencing of metastasis was not done due to bone only disease and other treatment options left.
• 4th line of therapy – capecitabine looks promising considering that tumor marker is finally decreasing.

TAKE HOME MESSAGE: 
 

• frequent monitoring of patients on ribociclib is urgent 

• for safe and effective patient treatment: 

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• importance of patient‘s compliance with our follow up instructions